Endostatin is an endogenous angiogenesis inhibitor isolated and purified from supernate of cultured mouse endothelioma (EOMA) by O'Reilly et al., in 1997. It is derived from the hydrolysate of type XVIII collagen, with a molecular weight of 20 kD. As demonstrated by experiments, endostatin inhibits blood vessel endothelium and tumor cells. Because of the difficulties such as renaturation of the recombinant endostatin, EntreMed Inc. (USA) gave up clinical research for the recombinant endostatin. And currently it is unable to prepare endostatin having a relatively high in vitro activity in large quantities.
In endostatin, the three histidines at positions 1, 3 and 11 at the N terminus and the Asp residue at position 76 together form a zinc ion binding site. Binding to zinc ion is crucial for the activity of endostatin. It is reported that the polypeptide from the N terminus of endostatin exhibits a certain activity in inhibiting vascular endothelial cell and tumor cell (Cancer Res. 2005; 65(9):3656-63; U.S. Pat. No. 7,524,811 B2). However, the experiments also show that the polypeptide containing amino acid residues 1-25 of the N terminus of the human endostatin could not significantly inhibit growth of tumor from human source implanted in mouse model. Activity of the endostatin-derived polypeptides is still needed to be improved.